September 19, 2012 ~ Last January, after a five-fold increase in complications was noted by the U.S. Food and Drug Administration (FDA) concerning synthetic mesh used in women to treat pelvic organ prolapse (POP) and stress urinary incontinence (SUI), the FDA ordered mesh makers to find out why.
At the time, the unprecedented request was seen as the agency flexing of its muscle, which it has the authority to do under Section 522.
“The 522 Postmarket Surveillance Studies Program encompasses design, tracking, oversight, and review responsibilities for studies mandated under section 522 of the Federal Food, Drug and Cosmetic Act. The program helps ensure that well-designed 522 postmarket surveillance (PS) studies are conducted effectively and efficiently and in the least burdensome manner.”
“Least burdensome” refers to the medical device manufacturer, not the patient who may have suffered injuries associated with that medical device.
Altogether the January 3 orders would encompass:
* 88 postmarket study orders to 33 manufacturers of urogynecologic surgical mesh for POP; and
* 11 postmarket study orders to seven manufacturers of single-incision mini-slings for SUI.
The studies were to answer some of the following questions about the severe and life-altering complications that were emerging among women treated for the relatively minor conditions of POP and SUI.
The mesh makers were to find out: the rates of mesh exposure, mesh erosion into another organ, pelvic pain, infection, dyspareunia, vaginal shortening, vaginal scarring, vaginal bleeding, fistula formation, neuromuscular problems, revision surgeries, quality of life, and recurrence of the problem, among other issues.
Women were to be followed for three years and adverse events reported at 6 months, 12, 18, 24 and 36.
Transvaginal and surgical mesh is not required to undergo safety and efficacy studies before it is marketed (under the agency’s 510(k) notification process), so these studies would provide the first look at what was going wrong.
MDND background story on mesh makers who received 522 orders here.
See a PDF link to two letters:
Letter - POP 522 Order – final – generic (2)-3 (pdf)
Letter - SUI 522 Order – final – generic (2)-1 (pdf)
“Within 30 days of receipt of this order, you must submit your plan to conduct postmarket surveillance of your device to the address listed below.”
A look at the website that follows the 522 plans (here) submitted by makers of various kinds of devices shows not much has happened.
“Plan pending” ‘Plan Overdue” “Other” and “Study Pending” indicate that postmarket surveillance does not happen quickly.
In addition when Ethicon, a division of Johnson & Johnson, announced in June it would remove four Gynecare meshes from the market, it also requested the agency abandon its request for the postmarket plans for those four - the TVT Secur, Prosima Pelvic Floor Repair System, Prolift Pelvic Floor Repair System, and the Prolift MTM Pelvic Floor Repair System.
In the case of metal-on-metal hip implant studies, requested in May 2011 for medical devices associated with a high failure rate, these too do not appear to be underway or have complied with the FDA 522 order, in that they say "plan overdue."
Sarah Clark-Lynn of the FDA’s Public Affairs Office told MDND last Friday, June 8, that the agency has “received Ethicon’s request and they have 60 days to respond.”
That means the FDA had until August 4th to issue an answer to Ethicon about the requirement to do expensive and time-consuming studies on four meshes it was planning to discontinue, though phasing out over the next 120 days.
Recently Clark-Lynn explained what the various designations mean:
MDND Q: What does 'plan pending,' 'study pending' and 'other' mean?
Plan PendingFDA has not approved the study plan, and it has been less than 6 months since issuance of the order.Plan OverdueFDA has not approved the study plan, and it has been 6 months or more since issuance of the order.Study PendingThe plan has been approved, but no subjects have been enrolled.OtherThe study status does not fit another category (e.g., change in ownership underway, redesigning device and need prior premarket clearance/approval to use in study, device has been cleared or approved but is not currently marketed). This is an interim study status.
Q: Since the various mesh makers had a limited time to get back to the FDA with a 522 study proposal, is there any action taken for non compliance?
“In January 2012, the FDA issued 99 orders for postmarket surveillance studies to manufacturers of surgical mesh used for as subset of treatments for pelvic organ prolapse and stress urinary incontinence. Manufacturers were required to submit a research protocol to the FDA that addresses specific safety issued related to these devices and outlined in the order. The FDA has received submissions from companies with these devices.
“As we move forward, the FDA will take the necessary compliance action when necessary."
Q: How many of the 99 orders/ how many companies/ have submitted 522 study plans to the satisfaction of the FDA?
“No submitted plans have been approved by FDA. The companies and FDA are working toward getting plans approved.”
Q: How do you define ‘out of compliance’ and what actions could be taken?
“The failure to have an approved postmarket surveillance plan or failure to conduct postmarket surveillance in accordance with the approved plan constitutes failure to comply with section 522 of the act. This may lead to actions such as seizure of product, injunction, prosecution, and/or civil money penalties.”
Q: It sounds like the request is being granted, but I don't like to speculate. As of today, has the FDA granted Ethicon's request not to have to produce 522 plans for its Gynecare products? The FDA had until August 4th to get back to Ethicon - Did it send a letter? Is it online or can I obtain it?
“FDA did send letters to Ethicon in response to their requests. FDA is amenable to Ethicon’s requests and is working with Ethicon based on the requests that were made. Please contact Ethicon to see if they would like to comment.”
Q: Can I see a copy of the FDA's letter to Ethicon which requested a pass on conducting the 522 studies? Can you scan it to me or is it available online? Since this was generated by the FDA, I think going to the agency is the appropriate place to make that request.
“You can request the letter through the FDA’s FOIA office.”
Q: When do you think these submitted 522 plans will be approved? Now that we are 9 months past the 522 request, what is the time frame by either the FDA or the manufacturers to be in compliance, or is there any time frame?
“We review each submission as it is provided to the FDA and make determinations for each one individually.”
Q: Can the public have access to the "plan," even through a FIOA request?
“The plans are proprietary information for the company. You may request them from the companies. In addition, you may submit a FOIA request for approved study plans and the non-proprietary information may be shared in that manner. You can find information on how to submit a request on our website.”
Q: Has a mesh manufacturer ever had its products seized, been subject to an injunction, been prosecuted or paid civil penalties?
”Given your deadline, I suggest searching the news releases posted on our website.”